Influence of Semaglutide on Pharmacokinetics and Pharmacodynamics of Warfarin and Pharmacokinetics of Metformin in Healthy Subjects

NCT02022254 | Completed Phase 1

• 3 other identifiers: NN9535-38172012-005072-33U1111-1136-6442
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This trial is conducted in Europe and Asia. The aim of the trial is to investigate the influence of semaglutide on pharmacokinetics (the exposure of the trial drug in the body) and pharmacodynamics (the effect of the investigated drug on the body) of warfarin and pharmacokinetics of metformin in healthy subjects.

Conditions

Diabetes; Diabetes Mellitus, Type 2; Healthy

Outcome Measures

Primary Outcomes (3)

• Area under the metformin plasma concentration-time curve

  During a dosing interval (0-12 hours) after the last of 7 repeated doses of metformin without semaglutide exposure (Day 4) and at semaglutide steady state (Day 104)

• Area under the S-warfarin plasma concentration-time curve

  From time 0 to 168 hours after a single dose of warfarin without semaglutide exposure (Day 11) and at semaglutide steady state (Day 111)

• Area under the R-warfarin plasma concentration-time curve

  From time 0 to 168 hours after a single dose of warfarin without semaglutide exposure (Day 11) and at semaglutide steady state (Day 111)

Secondary Outcomes (4)

• Maximum observed metformin plasma concentration at steady state

  From dosing until 30 hours after the last of 7 repeated doses without semaglutide exposure and at semaglutide steady state (metformin administration on Days 4 and 104)

• Maximum observed S-warfarin plasma concentration after single dose

  (0-168 hours) after a single dose of warfarin without semaglutide exposure and at semaglutide steady state (warfarin administrations on Days 11 and 111)

• Maximum observed R-warfarin plasma concentration after single dose

  (0-168 hours) after a single dose of warfarin without semaglutide exposure and at semaglutide steady state (warfarin administrations on Days 11 and 110)

• Incremental area under the INR (international normalised ratio) -curve

  From 0 to 168 hours

Study Arms (1)

Semaglutide administrations

EXPERIMENTAL

Drug: semaglutide; Drug: placebo; Drug: metformin; Drug: warfarin

Interventions

semaglutide DRUG

Subjects will initiate treatment with 0.25 mg for the first four weeks followed by dose doubling every four weeks up to a dose of 1.0 mg.

Semaglutide administrations

placebo DRUG

Semaglutide placebo will be administered s.c.

Semaglutide administrations

metformin DRUG

For oral administration twice daily, in two periods, each of 3.5 days duration. The first period is initiated before semaglutide treatment and the second period is initiated at the end of semaglutide treatment.

Semaglutide administrations

warfarin DRUG

For oral administration, given as a single dose. The first dose is given before semaglutide treatment and the second dose is given at the end of semaglutide treatment.

Semaglutide administrations

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female, age between 18 and 55 years (both inclusive) at the time of signing informed consent
• Body mass index (BMI) between 23 and 30 kg/m\^2 (both inclusive)

You may not qualify if:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearingpotential and not using adequate contraceptive methods for the duration of the trial and for 5 weeks following the last dose of semaglutide. Adequate contraceptive measures are implants, injectables, combined oral contraceptives, hormonal intrauterine device, sexual abstinence or vasectomised partner
• Any clinically significant disease history, in the opinion of the investigator, or systemic or organ disease including: pulmonary, gastrointestinal, hepatic, neurologic, renal, genitourinary and endocrine, dermatologic or hematologic diseases
• Use of prescription or non-prescription systemic or topical medicinal products (including routine or non-routine vitamins or herbal products, but excluding paracetamol and contraceptives) within 3 weeks (or within 5 half-lives of the medicinal product, whichever is longest) prior to Visit 2
• Smoking, drug or alcohol abuse

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (1)

Novo Nordisk Investigational Site

Berlin, 10117, Germany

Location

Related Publications (1)

• Hausner H, Derving Karsbol J, Holst AG, Jacobsen JB, Wagner FD, Golor G, Anderson TW. Effect of Semaglutide on the Pharmacokinetics of Metformin, Warfarin, Atorvastatin and Digoxin in Healthy Subjects. Clin Pharmacokinet. 2017 Nov;56(11):1391-1401. doi: 10.1007/s40262-017-0532-6.

  PMID: 28349387 RESULT

Related Links

• Clinical Trials at Novo Nordisk

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 2

Interventions

semaglutide; Metformin; Warfarin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Global Clinical Registry (GCR, 1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2013
• First Posted: December 27, 2013
• Study Start: December 17, 2013
• Primary Completion: August 28, 2014
• Study Completion: August 28, 2014
• Last Updated: April 4, 2017

Record last verified: 2017-03

Locations

DE (1)